Transcriptional profiling of native, proliferative, and differentiated hNECs

In parallel, transcriptomic profiling demonstrated that air-liquid interface-differentiated hNECs closely recapitulate the molecular features of native nasal epithelium. Functionally, differentiated hNECs reproduced key properties of airway surface liquid (ASL) physiology and its dysregulation under inflammatory and CF conditions. Finally, we show that basal hNECs provide a robust and accessible source for induced pluripotent stem cell (iPSC) generation. hNEC-derived iPSCs exhibited canonical pluripotency features, differentiated efficiently into germ layer derivatives and lung progenitors, and displayed transcriptomic profiles indistinguishable from iPSCs generated from other somatic sources.

Together, these findings position hNECs as a versatile, patient-specific platform enabling ex vivo biomarker discovery, in vitro modeling of airway physiology, and generation of stem cell–based models, thereby expanding their utility for respiratory research and precision medicine.